Risk and Prognosis of Subsequent Primary Gastric Cancer

2022 ◽  
Author(s):  
Rongrong Wei ◽  
Xinyu Du ◽  
Jing Wang ◽  
Qi Wang ◽  
Xiaojie Zhu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Survivors ◽  
Cox Regression ◽  
Prognostic Impact ◽  
Cancer Specific Survival ◽  
Cancer History ◽  
Primary Gastric Cancer ◽  
Actual Observation ◽  
Increased Risk

Introduction: The incidence and prognostic impact of subsequent primary gastric cancer (GC) in a population of other cancer survivors is unclear. We aimed to evaluate susceptibility to subsequent primary GC in cancer survivors and prognosis of GC with prior cancer history. Methods: 2,211 and 23,416 GC cases with and without prior cancer history were retrospectively selected from the Surveillance, Epidemiology and End Results (SEER) database. Potential risk of developing subsequent primary GC was assessed through standardized incidence ratios (SIRs). Cox regression were adopted to analyze the influence of prior cancer history and clinical characteristic factors on the prognosis of subsequent primary GC. A nomogram was established to predict overall survival (OS). Propensity score matching (PSM) was conducted to eliminate possible bias. Results: Compared with general population, cancer survivors had an increased risk of subsequent primary GC (SIR 1.17, 95% CI 1.15-1.20, P<0.05). Prior cancer history was related to poor OS of GC [adjusted hazard ratio (aHR) 1.12, 95% CI 1.06-1.19, P<0.001], but not cancer-specific survival (aHR 0.97, 95% CI 0.89-1.05, P=0.441). In addition, age, grade, stage, year of diagnosis, surgery, TNM stage and tumor size were independent prognostic factors for OS in GC cases with prior cancers. The concordance index of the nomogram was 0.72 (95% CI 0.71-0.74), and calibrate curves showed good agreement between prediction by the nomogram and actual observation. Conclusions: Cancer survivors with increased risk of developing subsequent primary GC should strengthen their monitoring and follow-up to prevent occurrence of subsequent primary gastric cancer.

scholarly journals Increased risk of cardiac ischaemia in a pan-European cohort of 36 205 childhood cancer survivors: a PanCareSurFup study

Heart ◽  
2020 ◽  
Vol 107 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Elizabeth Arnoldina Maria Feijen ◽  
Elvira C van Dalen ◽  
Heleen J H van der Pal ◽  
Raoul C Reulen ◽  
David L Winter ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Cumulative Incidence ◽  
Cox Regression ◽  
Childhood Cancer Survivors ◽  
Cardiac Ischaemia ◽  
Number Of Patients ◽  
Increased Risk

ObjectiveIn this report, we determine the cumulative incidence of symptomatic cardiac ischaemia and its risk factors among European 5-year childhood cancer survivors (CCS) participating in the PanCareSurFup study.MethodsEight data providers (France, Hungary, Italy (two cohorts), the Netherlands, Slovenia, Switzerland and the UK) participating in PanCareSurFup ascertained and validated symptomatic cardiac events among their 36 205 eligible CCS. Data on symptomatic cardiac ischaemia were graded according to the Criteria for Adverse Events V.3.0 (grade 3–5). We calculated cumulative incidences, both overall and for different subgroups based on treatment and malignancy, and used multivariable Cox regression to analyse risk factors.ResultsOverall, 302 out of the 36 205 CCS developed symptomatic cardiac ischaemia during follow-up (median follow-up time after primary cancer diagnosis: 23.0 years). The cumulative incidence by age 60 was 5.4% (95% CI 4.6% to 6.2%). Men (7.1% (95% CI 5.8 to 8.4)) had higher rates than women (3.4% (95% CI 2.4 to 4.4)) (p<0.0001). Of importance is that a significant number of patients (41/302) were affected as teens or young adults (14–30 years). Treatment with radiotherapy/chemotherapy conferred twofold risk (95% CI 1.5 to 3.0) and cases in these patients appeared earlier than in CCS without treatment/surgery only (15% vs 3% prior to age 30 years, respectively (p=0.04)).ConclusionsIn this very large European childhood cancer cohort, we found that by age 60 years, 1 in 18 CCS will develop a severe, life-threatening or fatal cardiac ischaemia, especially in lymphoma survivors and CCS treated with radiotherapy and chemotherapy increases the risk significantly.

scholarly journals Prognostic Impact of Different Gleason Patterns on Biopsy Within Grade Group 4 Prostate Cancer

2021 ◽  
Author(s):  
Keiichiro Mori ◽  
Vidit Sharma ◽  
Eva M. Comperat ◽  
Shun Sato ◽  
Ekaterina Laukhtina ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Rank Test ◽  
Prognostic Impact ◽  
Grade Group ◽  
Cancer Specific Survival ◽  
Kaplan Meier ◽  
Pathologic Features ◽  
Increased Risk

Abstract Background Grade group (GG) 4 prostate cancer (PC) is considered a single entity; however, there are questions regarding prognostic heterogeneity. This study assessed the prognostic differences among various Gleason scores (GSs) classified as GG 4 PC on biopsy before radical prostatectomy (RP). Methods We conducted a multicenter retrospective study, and a total of 1791 patients (GS 3 + 5: 190; GS 4 + 4: 1557; and GS 5 + 3: 44) with biopsy GG 4 were included for analysis. Biochemical recurrence (BCR)-free survival, cancer-specific survival, and overall survival were analyzed using the Kaplan–Meier method and the log-rank test. Logistic regression analysis was performed to identify factors associated with high-risk surgical pathologic features. Cox regression models were used to analyze time-dependent oncologic endpoints. Results Over a median follow-up of 75 months, 750 patients (41.9%) experienced BCR, 146 (8.2%) died of any causes, and 57 (3.2%) died of PC. Biopsy GS 5 + 3 was associated with significantly higher rates of GS upgrading in RP specimens than GS 3 + 5 and GS 4 + 4. On multivariable analysis adjusted for clinicopathologic features, different GSs within GG 4 were significantly associated with BCR (p = 0.03) but not PC-specific or all-cause mortality. Study limitations include the lack of central pathological specimen evaluation. Conclusions Patients with GG 4 at biopsy exhibited some limited biological and clinical heterogeneity. Specifically, GS 5 + 3 had an increased risk of GS upgrading. This can help individualize patients’ counseling and encourage further study to refine biopsy specimen-based GG classification.

scholarly journals Mediating Effects of Frailty Indicators on the Risk of Sepsis After Cancer

2018 ◽  
Vol 35 (7) ◽  
pp. 708-719 ◽  
Author(s):  
Justin Xavier Moore ◽  
Tomi Akinyemiju ◽  
Alfred Bartolucci ◽  
Henry E. Wang ◽  
John Waterbor ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cancer Survivors ◽  
Racial Differences ◽  
Cancer Survivorship ◽  
Cox Regression ◽  
Mediation Effect ◽  
Cancer History ◽  
Mediation Effects ◽  
Increased Risk ◽  
Using Data

Background: Cancer survivors are at increased risk of sepsis, possibly attributed to weakened physiologic conditions. The aims of this study were to examine the mediation effect of indicators of frailty on the association between cancer survivorship and sepsis incidence and whether these differences varied by race. Methods: We performed a prospective analysis using data from the REasons for Geographic and Racial Differences in Stroke cohort from years 2003 to 2012. We categorized frailty as the presence of ≥2 frailty components (weakness, exhaustion, and low physical activity). We categorized participants as “cancer survivors” or “no cancer history” derived from self-reported responses of being diagnosed with any cancer. We examined the mediation effect of frailty on the association between cancer survivorship and sepsis incidence using Cox regression. We repeated analysis stratified by race. Results: Among 28 062 eligible participants, 2773 (9.88%) were cancer survivors and 25 289 (90.03%) were no cancer history participants. Among a total 1315 sepsis cases, cancer survivors were more likely to develop sepsis (12.66% vs 3.81%, P < .01) when compared to participants with no cancer history (hazard ratios: 2.62, 95% confidence interval: 2.31-2.98, P < .01). The mediation effects of frailty on the log-hazard scale were very small: weakness (0.57%), exhaustion (0.31%), low physical activity (0.20%), frailty (0.75%), and total number of frailty indicators (0.69%). Similar results were observed when stratified by race. Conclusion: Cancer survivors had more than a 2-fold increased risk of sepsis, and indicators of frailty contributed to less than 1% of this disparity.

scholarly journals Return to Work in the Gastric Cancer Survivors

2021 ◽  
Author(s):  
Yuan-Yuei Chen ◽  
Wei-Liang Chen ◽  
Wei-Te Wu ◽  
Ching-Liang Ho ◽  
Chung-Ching Wang
Keyword(s):  
Gastric Cancer ◽  
Return To Work ◽  
Cancer Survivors ◽  
Cox Regression ◽  
Early Stage ◽  
Survival Outcomes ◽  
Kaplan Meier ◽  
Returning To Work ◽  
The Impact

Abstract Returning to work (RTW) is an often used outcome in work research to describe employee fully recovering from disease. Several factors are suggested as barriers for workers returning to work. The goal of this study was to investigate the role of RTW in workers with gastric cancer and identify its impact on their survival outcomes during 11 years of follow-up. A total of 4467 workers who with newly diagnosis of gastric cancer were included in this retrospective cohort study with a follow-up period ranging from 2004 to 2015. Relationships between work, treatment, and disease-related variables and RTW were analyzed by Cox regression. The impact of RTW on survival outcomes was analyzed by Kaplan-Meier survival curves. Old age, males, comorbidities, chemotherapy, radiotherapy, and manual jobs were inversely associated with RTW. Operation and early stage of gastric cancer were associated with increased likelihood of RTW. After adjusting for variables, workers with stage 1 gastric cancer were more likely return to work than other stages with HR of 4.67 (95%CI: 2.99~7.31) and 7.44 (95%CI: 4.12~13.43) in the 2nd and 5th year. In terms of effect of RTW on survival rate, reemployed workers had better survival than those without employment in all gastric cancer survivors. Furthermore, RTW had significant association with reduced risk of all-cause mortality (HR: 0.49, 95%CI: 0.38~0.65). Improving these identified barriers and strengthening facilitators of RTW can provide employers and government to conduct comprehensive employment plans for increasing the percentage of RTW in the gastric cancer survivors.

scholarly journals Elevated Expression of Glycerol-3-Phosphate Phosphatase as a Biomarker of Poor Prognosis and Aggressive Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1273
Author(s):  
Mohamed Amine Lounis ◽  
Veronique Ouellet ◽  
Benjamin Péant ◽  
Christine Caron ◽  
Zhenhong Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Biochemical Recurrence ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Specific Antigen ◽  
Metabolic Stress ◽  
Cancer Specific Survival ◽  
High Risk Prostate Cancer ◽  
Increased Risk

The limitations of the biomarker prostate-specific antigen (PSA) necessitate the pursuit of biomarkers capable of better identifying high-risk prostate cancer (PC) patients in order to improve their therapeutic management and outcomes. Aggressive prostate tumors characteristically exhibit high rates of glycolysis and lipogenesis. Glycerol 3-phosphate phosphatase (G3PP), also known as phosphoglycolate phosphatase (PGP), is a recently identified mammalian enzyme, shown to play a role in the regulation of glucose metabolism, lipogenesis, lipolysis, and cellular nutrient-excess detoxification. We hypothesized that G3PP may relieve metabolic stress in cancer cells and assessed the association of its expression with PC patient prognosis. Using immunohistochemical staining, we assessed the epithelial expression of G3PP in two different radical prostatectomy (RP) cohorts with a total of 1797 patients, for whom information on biochemical recurrence (BCR), metastasis, and mortality was available. The association between biomarker expression, biochemical recurrence (BCR), bone metastasis, and prostate cancer-specific survival was established using log-rank and multivariable Cox regression analyses. High expression of G3PP in PC epithelial cells is associated with an increased risk of BCR, bone metastasis, and PC-specific mortality. Multivariate analysis revealed high G3PP expression in tumors as an independent predictor of BCR and bone metastasis development. High G3PP expression in tumors from patients eligible for prostatectomies is a new and independent prognostic biomarker of poor prognosis and aggressive PC for recurrence, bone metastasis, and mortality.

scholarly journals Risk of infective endocarditis among patients with tetralogy of fallot

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Havers-Borgersen ◽  
J.H Butt ◽  
M Groening ◽  
M Smerup ◽  
G.H Gislason ◽  
...  
Keyword(s):  
Infective Endocarditis ◽  
Tetralogy Of Fallot ◽  
Valve Replacement ◽  
Pulmonary Valve ◽  
Cox Regression ◽  
Pulmonary Valve Replacement ◽  
Varying Coefficients ◽  
Background Population ◽  
Increased Risk

Abstract Introduction Patients with tetralogy of Fallot (ToF) are considered at high risk of infective endocarditis (IE) as a result of altered hemodynamics and multiple surgical and interventional procedures including pulmonary valve replacement (PVR). The overall survival of patients with ToF has increased in recent years. However, data on the risk of adverse outcomes including IE are sparse. Purpose To investigate the risk of IE in patients with ToF compared with controls from the background population. Methods In this nationwide observational cohort study, all patients with ToF born in 1977–2017 were identified using Danish nationwide registries and followed from date of birth until occurrence of an outcome of interest (i.e. first-time IE), death, or end of study (July 31, 2017). The comparative risk of IE among ToF patients versus age- and sex-matched controls from the background population was assessed. Results A total of 1,156 patients with ToF were identified and matched with 4,624 controls from the background population. Among patients with ToF, 266 (23.0%) underwent PVR during follow-up. During a median follow-up time of 20.4 years, 38 (3.3%) patients and 1 (0.03%) control were admitted with IE. The median time from date of birth to IE was 10.8 years (25th-75th percentile 2.8–20.9 years). The incidence rates of IE per 1,000 person-years were 2.2 (95% confidence interval (CI) 1.6–3.0) and 0.01 (95% CI 0.0001–0.1) among patients and controls, respectively. In multivariable Cox regression models, in which age, sex, pulmonary valve replacement, and relevant comorbidities (i.e. chronic renal failure, diabetes mellitus, presence of cardiac implantable electronic devices, other valve surgeries), were included as time-varying coefficients, the risk of IE was significantly higher among patients compared with controls (HR 171.5, 95% CI 23.2–1266.7). Moreover, PVR was associated with an increased risk of IE (HR 3.4, 95% CI 1.4–8.2). Conclusions Patients with ToF have a substantial risk of IE and the risk is significantly higher compared with the background population. In particular, PVR was associated with an increased risk of IE. With an increasing life-expectancy of these patients, intensified awareness, preventive measures, and surveillance of this patient group are advisable. Figure 1. Cumulative incidence of IE Funding Acknowledgement Type of funding source: None

scholarly journals Urinary Carnosinase-1 Excretion is Associated with Urinary Carnosine Depletion and Risk of Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Cohort Study

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1102
Author(s):  
Angelica Rodriguez-Niño ◽  
Diego O. Pastene ◽  
Adrian Post ◽  
M. Yusof Said ◽  
Antonio W. Gomes-Neto ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Failure ◽  
Cox Regression ◽  
Carbonyl Stress ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Increased Risk ◽  
High Concentrations ◽  
Kidney Function Decline

Carnosine affords protection against oxidative and carbonyl stress, yet high concentrations of the carnosinase-1 enzyme may limit this. We recently reported that high urinary carnosinase-1 is associated with kidney function decline and albuminuria in patients with chronic kidney disease. We prospectively investigated whether urinary carnosinase-1 is associated with a high risk for development of late graft failure in kidney transplant recipients (KTRs). Carnosine and carnosinase-1 were measured in 24 h urine in a longitudinal cohort of 703 stable KTRs and 257 healthy controls. Cox regression was used to analyze the prospective data. Urinary carnosine excretions were significantly decreased in KTRs (26.5 [IQR 21.4–33.3] µmol/24 h versus 34.8 [IQR 25.6–46.8] µmol/24 h; p < 0.001). In KTRs, high urinary carnosinase-1 concentrations were associated with increased risk of undetectable urinary carnosine (OR 1.24, 95%CI [1.06–1.45]; p = 0.007). During median follow-up for 5.3 [4.5–6.0] years, 84 (12%) KTRs developed graft failure. In Cox regression analyses, high urinary carnosinase-1 excretions were associated with increased risk of graft failure (HR 1.73, 95%CI [1.44–2.08]; p < 0.001) independent of potential confounders. Since urinary carnosine is depleted and urinary carnosinase-1 imparts a higher risk for graft failure in KTRs, future studies determining the potential of carnosine supplementation in these patients are warranted.

scholarly journals Use of incretin-based drugs and risk of cholangiocarcinoma: Scandinavian cohort study

Diabetologia ◽  
2021 ◽  
Author(s):  
Peter Ueda ◽  
Viktor Wintzell ◽  
Mads Melbye ◽  
Björn Eliasson ◽  
Ann-Marie Svensson ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Cox Regression ◽  
Absolute Rate ◽  
Dipeptidyl Peptidase 4 ◽  
Rate Difference ◽  
Receptor Agonists ◽  
Dpp4 Inhibitors ◽  
Increased Risk ◽  
Increase In Risk

Abstract Aims/hypothesis Concerns have been raised regarding a potential association of use of the incretin-based drugs dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide-1 (GLP-1)-receptor agonists with risk of cholangiocarcinoma. We examined this association in nationwide data from three countries. Methods We used data from nationwide registers in Sweden, Denmark and Norway, 2007–2018, to conduct two cohort studies, one for DPP4 inhibitors and one for GLP-1-receptor agonists, to investigate the risk of incident cholangiocarcinoma compared with an active-comparator drug class (sulfonylureas). The cohorts included patients initiating treatment episodes with DPP4 inhibitors vs sulfonylureas, and GLP-1-receptor agonists vs sulfonylureas. We used Cox regression models, adjusted for potential confounders, to estimate hazard ratios from day 366 after treatment initiation to account for cancer latency. Results The main analyses of DPP4 inhibitors included 1,414,144 person-years of follow-up from 222,577 patients receiving DPP4 inhibitors (median [IQR] follow-up time, 4.5 [2.6–7.0] years) and 123,908 patients receiving sulfonylureas (median [IQR] follow-up time, 5.1 [2.9–7.8] years) during which 350 cholangiocarcinoma events occurred. Use of DPP4 inhibitors, compared with sulfonylureas, was not associated with a statistically significant increase in risk of cholangiocarcinoma (incidence rate 26 vs 23 per 100,000 person-years; adjusted HR, 1.15 [95% CI 0.90, 1.46]; absolute rate difference 3 [95% CI -3, 10] events per 100,000 person-years). The main analyses of GLP-1-receptor agonists included 1,036,587 person-years of follow-up from 96,813 patients receiving GLP-1-receptor agonists (median [IQR] follow-up time, 4.4 [2.4–6.9] years) and 142,578 patients receiving sulfonylureas (median [IQR] follow-up time, 5.5 [3.2–8.1] years) during which 249 cholangiocarcinoma events occurred. Use of GLP-1-receptor agonists was not associated with a statistically significant increase in risk of cholangiocarcinoma (incidence rate 26 vs 23 per 100,000 person-years; adjusted HR, 1.25 [95% CI 0.89, 1.76]; absolute rate difference 3 [95% CI -5, 13] events per 100,000 patient-years). Conclusions/interpretation In this analysis using nationwide data from three countries, use of DPP4 inhibitors and GLP-1-receptor agonists, compared with sulfonylureas, was not associated with a significantly increased risk of cholangiocarcinoma. Graphical abstract

Prevalence and prognostic impact of somatic mutations in patients with heart failure and reduced ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D.J Vazquez Andres ◽  
A Hernandez Vicente ◽  
M Diez Diez ◽  
M Gomez Molina ◽  
A Quintas ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Somatic Mutations ◽  
Myocardial Dysfunction ◽  
Study Endpoint ◽  
Prognostic Impact ◽  
Reduced Ejection Fraction ◽  
Increased Risk ◽  
Patients With Heart Failure

Abstract Introduction Somatic mutations in hematopoietic cells are associated with age and have been associated with higher mortality in apparently healthy adults, especially due to atherosclerotic disease. In animal models, somatic mutations are associated with atherosclerosis progression and myocardial dysfunction, especially when gene TET2 is affected. Preliminary clinical data, referred to ischemic heart failure (HF), have associate the presence of these acquired mutations with impaired prognosis. Purpose To study the prevalence of somatic mutations in patients with heart failure with reduced ejection fraction (HFrEF) and their impact on long-term prognosis. Methods We studied a cohort of elderly patients (more than 60 years old) hospitalized with HFrEF (LVEF&lt;45%). The presence of somatic mutations was assessed using next generation sequencing (Illumina HiSeq 2500), with a mutated allelic fraction of at least 2% and a panel of 55 genes related with clonal hematopoiesis. Patients were followed-up for a median of three years. The study endpoint was a composite of death or readmission for worsening HF. Kaplan-Meier analysis (log-rank test) and Cox proportional hazards regression models were performed adjusting for age, sex and LVEF. Results A total of 62 patients (46 males (74.2%), age 74±7.5 years) with HFrEF (LVEF 29.7±7.8%) were enrolled in the study. The ischemic etiology was present in 54% of patients. Somatic mutations in Dnmt3a or Tet2 were present in 11 patients (17.7%). No differences existed in baseline characteristics except for a higher prevalence of atrial fibrillation in patients with somatic mutations (70% vs. 40%, p=0.007). During the follow-up period, 40 patients (64.5%) died and 38 (61.3%) had HF re-admission. The KM survival analysis for the combined event is shown in Figure 1. Compared with patients without somatic mutations and after adjusting for covariates, there was an increased risk of adverse outcomes when the somatic mutations were present (HR 3.6, 95% CI [1.6, 7.8], p=0.0014). This results remains considering death as a competing risk (Gray's test p=0.0097) and adjusting for covariates (HR = 2.21 95% CI [0.98, 5], p=0.0556). Conclusions Somatic mutation are present in patients with HFrEF and determine a higher risk of adverse events in the follow-up. Further studies are needed to assess the clinical implications of these findings. Figure 1 Funding Acknowledgement Type of funding source: None

Global longitudinal strain predicts outcome in chronic heart failure across American Heart Association stages: results from the MyoVasc study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S.O Troebs ◽  
A Zitz ◽  
S Schwuchow-Thonke ◽  
A Schulz ◽  
M.W Heidorn ◽  
...  
Keyword(s):  
American Heart Association ◽  
Prognostic Value ◽  
Longitudinal Strain ◽  
American Heart ◽  
Cox Regression ◽  
Global Longitudinal Strain ◽  
Heart Association ◽  
Increased Risk ◽  
Systolic And Diastolic Function

Abstract Background Global longitudinal strain (GLS) demonstrated a superior prognostic value over left ventricular ejection fraction (LVEF) in acute heart failure (HF). Its prognostic value across American Heart Association (AHA) stages of HF – especially under considering of conventional echocardiographic measures of systolic and diastolic function – has not yet been comprehensively evaluated. Purpose To evaluate the prognostic value of GLS for HF-specific outcome across AHA HF stages A to D. Methods Data from the MyoVasc-Study (n=3,289) were analysed. Comprehensive clinical phenotyping was performed during a five-hour investigation in a dedicated study centre. GLS was measured offline utilizing QLab 9.0.1 (PHILIPS, Germany) in participants presenting with sinus rhythm during echocardiography. Worsening of HF (comprising transition from asymptomatic to symptomatic HF, HF hospitalization, and cardiac death) was assessed during a structured follow-up with subsequent validation and adjudication of endpoints. AHA stages were defined according to current guidelines. Results Complete information on GLS was available in 2,400 participants of whom 2,186 categorized to AHA stage A to D were available for analysis. Overall, 434 individuals were classified as AHA stage A, 629 as stage B and 1,123 as stage C/D. Mean GLS increased across AHA stages of HF: it was lowest in stage A (−19.44±3.15%), −18.01±3.46% in stage B and highest in AHA stage C/D (−15.52±4.64%, P for trend &lt;0.0001). During a follow-up period of 3.0 [1.3/4.0] years, GLS denoted an increased risk for worsening of HF after adjustment for age and sex (hazard ratio, HRGLS [per standard deviation (SD)] 1.97 [95% confidence interval 1.73/2.23], P&lt;0.0001) in multivariable Cox regression analysis. After additional adjustment for cardiovascular risk factors, clinical profile, LVEF and E/E' ratio, GLS was the strongest echocardiographic predictor of worsening of HF (HRGLS [per SD] 1.47 [1.20/1.80], P=0.0002) in comparison to LVEF (HRLVEF [per SD] 1.23 [1.02/1.48], P=0.031) and E/E' ratio (HRE/E' [per SD] 1.12 [0.99/1.26], P=0.083). Interestingly, when stratifying for AHA stages, GLS denoted a similar increased risk for worsening of HF in individuals classified as AHA stage A/B (HRGLS [per SD] 1.63 [1.02/2.61], P=0.039) and in those classified as AHA stage C/D (HRGLS [per SD] 1.95 [1.65/2.29], P&lt;0.0001) after adjustment for age and sex. For further evaluation, Cox regression models with interaction analysis indicated no significant interaction for (i) AHA stage A/B vs C/D (P=0.83) and (ii) NYHA functional class &lt;II vs ≥II in individuals classified as AHA stage C/D (P=0.12). Conclusions GLS demonstrated a higher predictive value for worsening of HF than conventional echocardiographic measures of systolic and diastolic function. Interestingly, GLS indicated an increased risk for worsening of HF across AHA stages highlighting its potential value to advance risk prediction in chronic HF. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): German Center for Cardiovascular Research (DZHK), Center for Translational Vascular Biology (CTVB) of the University Medical Center of the Johannes Gutenberg-University Mainz

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